A. The panel illustrates an unrooted phylogenetic tree of the human nuclear steroid receptors. The phylogenetic tree was obtained following alignment of the amino acid sequences of the indicated nuclear receptors using the Clustal-omega algorithm (Sievers F, Wilm A, Dineen DG, Gibson TJ, Karplus K, Li W, Lopez R, McWilliam H, Remmert M, Söding J, Thompson JD, Higgins D. Fast, scalable generation of high-quality protein multiple sequence alignments using Clustal Omega Molecular Systems Biology 7 Article number: 539 doi:10.1038/msb.2011.75) B. The schematic structure of a typical nuclear receptor (NR) is shown in the upper diagram. The N-terminal A- and B-regions are responsible for the ligand-independent activation function (AF-1). The C-region contains the DNA-binding domain, while the unstructured D-region connects the C- and E-regions. The E-region containing the ligand-binding pocket is responsible for the ligand-dependent activation function (AF-2). The function of the C-terminal F-region is undefined. The tridimensional structure of the C- and E-regions contained in a representative NR (ERα) is illustrated in the lower part of the figure.